The orphan nuclear receptor Rev-erbalpha: a transcriptional link between circadian rhythmicity and cardiometabolic disease

Curr Opin Lipidol. 2007 Apr;18(2):141-6. doi: 10.1097/MOL.0b013e3280464ef6.


Purpose of review: This review focuses on recent advances on the role of the orphan nuclear receptor Rev-erbalpha, a transcription factor participating in the control of circadian rhythm and cardiometabolic disease.

Recent findings: Circadian patterns of cardiovascular vulnerability are well documented, with a peak incidence of cardiovascular events in the morning. Recent studies have outlined the importance of the Clock genes in the development of metabolic disorders predisposing to atherosclerosis. Rev-erbalpha is a nuclear receptor that regulates hepatic and adipose lipid metabolism as well as vascular inflammation. Moreover, Rev-erbalpha is also part of the clock transcription machinery and the target of some clock transcription factors.

Summary: These findings identify Rev-erbalpha as a modulator of cardiovascular risk factors and as a determinant of the circadian regulation of metabolic pathways. Moreover, Rev-erbalpha crosstalks with other nuclear receptors which influence atherosclerosis susceptibility. Rev-erbalpha may thus serve to integrate metabolic and circadian signals.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Clocks / genetics
  • CLOCK Proteins
  • Circadian Rhythm*
  • DNA-Binding Proteins / metabolism
  • Heart Diseases / metabolism*
  • Humans
  • Metabolic Diseases / metabolism*
  • Mice
  • Models, Biological
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Nr1d1 protein, mouse
  • Nuclear Receptor Subfamily 1, Group D, Member 1
  • Receptors, Cytoplasmic and Nuclear
  • Trans-Activators
  • Transcription Factors
  • CLOCK Proteins
  • CLOCK protein, human
  • Clock protein, mouse